Effects of PFBS exposure on adverse pregnancy outcomes and fetal development. Perfluorobutane sulfonate (PFBS) is a new chemical widely used in industrial and household products and its persistence, bioaccumulation and toxic properties has been reported. The scientific aims of this proposal are based on the toxicity of PFBS and our preliminary findings that exposure to PFBS can lead to pregnancy- induced hypertension (PIH) and altered maternal and fetal thyroid hormone levels in a Shanghai Birth Cohort (SBC) led by my primary mentor, Dr. Jun Jim Zhang. The prevalence of PIH (~10%) is high in China and PIH- related complications are still threatening maternal and fetal life and health worldwide due to the lack of efficient therapeutic methods. Epidemiology studies have pointed to a thyroid-related disease outbreak in China, especially women are at higher risk of developing hypothyroidism (~17%). Proper thyroid hormone levels are critical for fetal growth and maintaining pregnancy. Environmental exposures including PFBS can contribute to these adverse outcomes. Therefore, the major aim of this proposal is to investigate the effect of maternal exposure to PFBS on the risk of PIH and maternal and cord blood levels of thyroid hormones in Shanghai. We also propose to investigate the underline mechanisms of these findings. A key innovation is that we will answer critical and novel epidemiological and biological research questions. The molecular biology assays for studying mechanisms are innovative, especially the genome-wide chromatin accessibility which is a novel and the most advanced approach to study epigenetics. Successful completion of these aims builds on my expertise (strong molecular biology training and research experiences in maternal fetal medicine) and extends it to exposure assessment and reproductive and perinatal epidemiology in a global research setting that requires additional training and mentorship. I will attain the necessary expertise by working with experts in the relevant fields, through formal course work, structured mentored training and laboratory work. This project will take advantage of the available infrastructure in Shanghai through the highly respected LMIC research institution that will enable me to establish a pregnancy cohort of 6,500-10,000 women and follow the newborns up to two years at a cost effective efficient manner. This grant, beyond providing the necessary training to me to be established as an independent international researcher, will address important gaps in evidence on the effects of PFBS exposure on maternal and child health, and will provide a resource for future studies.